ArticleACS chemical neuroscience2016
Development of Sulfonamide Photoaffinity Inhibitors for Probing Cellular γ-Secretase.
Article in ACS chemical neuroscience, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 24 citations in OpenAlex.
- Ligand discovery by activity-based protein profiling.Cell chemical biology · 2024Review
- Design and Evaluation of a Cyclobutane Diazirine Alkyne Tag for Photoaffinity Labeling in Cells.Journal of the American Chemical Society · 2022Article
- γ-Secretase in Alzheimer's disease.Experimental & molecular medicine · 2022Review
- Imaging of Cancer γ-Secretase Activity Using an Inhibitor-Based PET Probe.Clinical cancer research : an official journal of the American Association for Cancer Research · 2021Article
- Article
- γ-Secretase inhibitors and modulators: Mechanistic insights into the function and regulation of γ-Secretase.Seminars in cell & developmental biology · 2020Review
- Structure-activity relationships of sulfonamides derived from carvacrol and their potential for the treatment of Alzheimer's disease.RSC medicinal chemistry · 2020Article
- Clickable photoaffinity ligands for the human serotonin transporter based on the selective serotonin reuptake inhibitor (S)-citalopram.Bioorganic & medicinal chemistry letters · 2018Article
- Current advances of carbene-mediated photoaffinity labeling in medicinal chemistry.RSC advances · 2018Review
- Mapping the Binding Site of BMS-708163 on γ-Secretase with Cleavable Photoprobes.Cell chemical biology · 2017Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
γ-Secretase is a multiprotein complex that catalyzes intramembrane proteolysis associated with Alzheimer's disease and cancer. Here, we have developed potent sulfonamide clickable photoaffinity probes that target γ-secretase in vitro and in cells by incorporating various photoreactive groups and walking the clickable alkyne handle to different positions around the molecule. We found that benzophenone is preferred over diazirine as a photoreactive group within the sulfonamide scaffold for labeling γ-secretase. Intriguingly, the placement of the alkyne at different positions has little effect on probe potency but has a significant impact on the efficiency of labeling of γ-secretase. Moreover, the optimized clickable photoprobe, 163-BP3, was utilized as a cellular probe to effectively assess the target engagement of inhibitors with γ-secretase in primary neuronal cells. In addition, biotinylated 163-BP3 probes were developed and used to capture the native γ-secretase complex in the 3-[(3-cholamidopropyl)dimethylammonio]-2-hydroxy-1-propanesulfonate (CHAPSO) solubilized state. Taken together, these next generation clickable and biotinylated sulfonamide probes offer new tools to study γ-secretase in biochemical and cellular systems. Finally, the data provide insights into structural features of the sulfonamide inhibitor binding site in relation to the active site and into the design of clickable photoaffinity probes.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.